Research on heart disease in the 196Os and 197Os was primarily concerned with risk factors for "premature" atherosclerosis, which was most dramatically apparent in working middle-aged men who suffered heart attacks or died suddenly. This focus on "premature" disease was an important initial step, but it resulted in a relative neglect of studies in older adults and in all women. Coronary heart disease remains nonetheless a major cause of morbidity and mortality among women. The primary goal of this project is to evaluate the safety of calcium-channel blockers in the secondary prevention of myocardial infarction in women. Given the consistent findings from clinical trials that calcium-channel blockers administered following myocardial infarction do not decrease the risk of death or reinfarction, and that some drugs of this class may actually increase the risk, it is unlikely that future trials of this therapy in women will be conducted. Yet the calcium-channel blockers are used with increasing frequency in women following myocardial infarction. The only ethical method of conducting studies of the safety of these drugs in women is through observational studies. On-going studies of hormone-replacement therapy in women at Group Health Cooperative of Puget Sound (GHC) have identified all female enrollees who suffered a first heart attack since 1986; the proposed project will expand this inception cohort through 1996. Information from medical record review and GHC databases will be used to assess risk factors and co-morbid conditions both at entry into the cohort and during up to l0 years of follow-up, and to identify recurrent cardiovascular events and deaths. A complete record of prescription drug exposure during the follow-up period will be obtained for each subject from the GHC computerized pharmacy database. Although the main hypothesis relates to reinfarction risk in women, men will be studied as well to facilitate comparison of the results of this observational study with those of the clinical trials. According to conservative estimates of the available sample size, we will have 86% power to detect a relative risk of 1.45 in women alone, and 85% power to detect a relative risk of 1.25 in men and women combined, for the association of calcium-channel blocker use with fatal or non-fatal reinfarction. With only the additional work required to do the appropriate analyses, this project will also examine the safety and efficacy of other cardiovascular drugs commonly used in women after myocardial infarction, and these include angiotensin converting-enzyme inhibitors, lipid-lowering drugs, and estrogen replacement therapy. Data from observational studies such as the one proposed can help to guide clinical practice and can assist in the design of appropriate secondary prevention trials ill women.